Outbreak of West Nile virus infection among humans in Serbia, August to October 2012.

We describe the first reported outbreak of West Nile virus (WNV) infection in humans in Serbia in August to October 2012 and examine the association of various variables with encephalitis and fatal outcome. Enzyme-linked immunosorbent assay (ELISA) was used for detection of WNV-specific IgM and IgG antibodies in sera and cerebrospinal fluid. A total of 58 patients (mean age: 61 years; standard deviation: 15) were analysed: 44 were from Belgrade and its suburbs; 52 had neuroinvasive disease, of whom 8 had meningitis, while 44 had encephalitis. Acute flaccid paralysis developed in 13 of the patients with encephalitis. Age over 60 years and immunosuppression (including diabetes) were independently associated with the development of encephalitis in a multivariate analysis: odds ratio (OR): 44.8 (95% confidence interval (CI): 4.93­408.59); p=0.001 (age over 60 years); OR: 10.76 (95% CI: 1.06­109.65); p=0.045 (immunosuppression including diabetes). Respiratory failure requiring mechanical ventilation developed in 13 patients with encephalitis. A total of 35 patients had completely recovered by the time they were discharged; nine patients died. The presence of acute flaccid paralysis, consciousness impairment, respiratory failure and immunosuppression (without diabetes) were found to be associated with death in hospital in a univariate analysis (p<0.001, p=0.007, p<0.001 and p=0.010, respectively).

Imported parasitic infections in Serbia.

BACKGROUND: Travel to the tropics is associated with a risk of parasitic infection, which is increasing in parallel with the rise in travel to these areas. We thus examined the prevalence and trend in the occurrence of parasitic infections in Serbian travelers. METHODS: A retrospective analysis of the medical records of all travelers returning from tropical and subtropical areas, who presented at the Institute for Infectious and Tropical Diseases in Belgrade between January 2001 and January 2008, was performed. RESULTS: Of a total of 2440 travelers, 169 (6.9%) were diagnosed with a parasitic infection, including malaria in 79, intestinal parasites in 84 (pathogenic species in 30 and non-pathogenic in 54), filariasis in four, and visceral leishmaniasis and fascioliasis in one patient each. Importantly, of the whole series only 583 (23.9%) were symptomatic, of which 19.4% were found to be infected with a parasite. The single pathogenic parasite occurring in asymptomatic patients was Giardia intestinalis. CONCLUSIONS: Parasitic infection causing symptomatic disease among travelers returning from tropical areas to Serbia is not infrequent. In view of the expected increase in travel to the tropics, diagnostic protocols for tropical parasitic diseases should take these data into account.

Seasonality of trichinellosis in patients hospitalized in Belgrade, Serbia.

A retrospective study of the course and outcome of trichinellosis in a series of 50 patients hospitalized at the Institute for Infectious and Tropical Diseases in Belgrade between 2001 and 2008 was performed. Clinical diagnosis of trichinellosis was based upon the patients' clinical history, symptoms and signs, and eosinophilia. The occurrence of cases showed a strong seasonality (P < 0.0001). The incubation period ranged between one and 33 days. The mean time between onset of symptoms and admission was nine days. Family outbreaks were the most frequent. Smoked pork products were the dominant source of infection (76%). Fever was the most frequent clinical manifestation (90%), followed by myalgia (80%) and periorbital edema (76%). 43 patients were examined serologically and 72% of them had anti-Trichinella antibodies. Eosinophilia and elevated levels of serum CK and LDH were detected in 94, 50 and 56% of the patients, respectively. All patients responded favorably to treatment with mebendazole or albendazole, but eight developed transient complications. Trichinellosis remains a major public health issue in Serbia.

Epidemiology and diagnostics of visceral leishmaniasis in Serbia.

A retrospective epidemiological and diagnostic study of visceral leishmaniasis (VL) was carried out during the period 2001-2007 and included patients suspected of VL who had been diagnosed at the Parasitological Laboratory at the Institute for Infectious and Tropical Diseases, Belgrade. Diagnosis of VL was confirmed by microscopic examination of Giemsa-stained bone marrow (BM) smears. BM smears from 134 patients were examined; 22 cases of VL were diagnosed, the majority of which involved individuals who had been on holiday at the Montenegrian sea coast. The sensitivity of the initial BM smears was inadequate; this required the application of a serological test, adapted for routine use, for the diagnosis of VL.

[Autoimmune hepatitis and/or hepatitis C]. / Autoimunski hepatitis i/ili hepatitis "C".

UNLABELLED: Hepatitis C virus (HCV) was identified in 1989 as a primary aetiologic agent of parenterally transmitted non-A non-B hepatitis and a major cause of acute and chronic hepatitis worldwide [1, 2]. Extrahepatic manifestations that are associated with chronic HCV infection include: type II cryoglobulinaemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, Sjogren syndrome, autoimmune thyroiditis, lichen planus, etc. [3, 4]. Likewise, there is a very interesting link between HCV and autoimmune hepatitis type I [5-7]. The second generation of immunoassays confirmed positive anti HCV in a relatively low percent of patients (0-5%) with autoimmune hepatitis type I [5-7]. This fact suggests that HCV infection is not an important factor in the pathogenesis of autoimmune hepatitis, but it is not excluded. The examination of autoimmune markers is highly significant for the proper decision of the therapy: interferon therapy leads to exacerbation of autoimmune hepatitis, while corticosteroids enhance virus replication in patients with HCV infection. There is a percentage of patients suffering from both diseases, and in this case the therapeutic strategy is the treatment of predominant disease. The aim of the study was to establish the proper diagnose and make an adequate therapeutic decision in HCV infection combined with positive autoantibody findings. PATIENTS AND METHODS: In our study forty nine patients with HCV infection of autoimmune markers are described. Diagnosis of HCV infection was confirmed by clinical, biochemical, serological and histological examinations. ANA, AMA, and ASMA as non-specific autoimmune markers have been studied. Significant titre of ANA is 1:80, AMA 1:40 and ASMA 1:20 or higher. The patients included in the study were HBsAg negative, anti-HCV positive (at least six months) and had no sign of any other chronic disease, such as Morbus Wilson, alpha-1-antitrypsin deficiency or haemochromatosis. RESULTS: The relevant data on patients are shown in Table 1. It is evident that 45% of patients had no known risk factors. The results of autoantibody are shown in Table 2. Eleven patients (22%) had autoantibodies, of whom one had 1:40 titre of ANA, while three had 1:80 titre of ASMA. Positive titre of AMA 1:40 was found in two patients. The distribution of relative autoantibody concentrations showed insignificant titres. The interferon therapy was used in five HCV RNA positive cases without progression. DISCUSSION: Pathologic immune responses are sometimes the primary cause of autoimmune disorder, and sometimes the second one. The best studied factors that produce autoimmune disorder, are viruses. Probably the best evidence of virus aetiology of autoimmune hepatitis is the presence of anti-HCV antibody in some patients with autoimmune hepatitis type 1. Our clinical trial revealed the presence of autoantibodies in 22% of patients who suffered from HCV infection. These results are very similar to those of other authors [3, 5, 6, 16]. From the clinical point of view all patients can be divided into three groups: 1) The first group consists of patients with false positive results of anti-HCV and "true" autoimmune hepatitis type 1. Corticosteroid treatment is recommended. 2) The second group consists of patients with HCV infection and low percent of autoantibodies titres. These patients should be treated with alpha-interferon. 3) The third group consists of patients suffering from both diseases: chronic hepatitis C and autoimmune hepatitis. In this case, the initial treatment should start with corticosteroids (as low risk therapy) but if the progression is still on, corticosteroids should be substituted by interferon therapy. Our patients belonged to the second group, because of nonspecific titres of relative autoantibody concentrations. Our conclusion was that none of these patients had autoimmune hepatitis but certain autoimmune phenomena. The interferon therapy was used in five HCV RNA positive cases without

[Neurologic manifestations in trichinosis]. / Neuroloske manifestacije u toku trihinoze.

Neurologic manifestations are present in about 10-20 percent of patients with trichinosis. They could be a serious diagnostic problem in the absence of corresponding epidemiological data and typical symptoms and signs of the disease. In untreated patients the mortality rate is about 50%. Several pathogenic mechanisms are responsible for the neurological complications in trichinosis: obstruction of brain blood vessels by larvae, cysts or granulomas, toxic vasculitis with secondary thrombosis and haemorrhages, granulomatous inflammation of the brain parenchyma and allergic reaction. Neurotrichinosis is manifested with clinical symptoms and signs of meningitis, encephalitis, polyradiculoneuritis, poliomyelitis, myastenia gravis, paresis and paralysis, with the clinical picture of systemic disease of the connective tissue involving the nervous system and, extremely rare, as a sinus thrombosis. Thus, the broad spectrum of neurological lesions in trichinosis is, probably, the results of the fact that Trichinella spiralis larvae, during haematogenic dissemination has no special affinity for particular parts of the nervous system. We present five patients with encephalitis and focal cerebral lesions in trichinosis. In one patient the neurologic manifestations were the only sign of the disease. We believe that all pathogenic mechanisms mentioned above, were involved in the onset of neurological manifestations in our patients. The diagnosis of the disease was based on the clinical picture, epidemiological data, microscopic identification of larvae in the muscular tissue, the presence of antibodies against Trichinella spiralis in cerebrospinal fluid (with preserved blood brain barrier) and in serum confirmed by IIF method, computerised tomography and magnetic resonance imaging of the brain, eosinophilia in the peripheral blood picture. One patient died, and in the remaining patients the course of the disease was favourable; they were discharged from the hospital with minimal neurologic sequelae.